The candidate's long-term career goal is to become an independent researcher who will integrate methods in genetic epidemiology with those used in health services and clinical epidemiology to improve the care of neonates. Respiratory Distress Syndrome (RDS) is the major cause of morbidity and mortality in premature infants. The primary etiology of the RDS is developmental immaturity of surfactant production. However, there is significant heterogeneity in pulmonary outcomes among infants of the same gestational age who have similar clinical risk factors. Studies suggest a significant genetic contribution to the risk of RDS. Genetic variations that are clinically insignificant among term infants may contribute to preterm infants' susceptibility to RDS. The specific aims of the proposal are 1) to examine if common genetic variations (single nucleotide polymorphisms) in the genes that code for Surfactant Proteins A, B, and C and ATP binding cassette transporter 3 are associated with RDS, and 2) to evaluate if severity of RDS is associated with these genetic variations. To accomplish these aims, we will employ a unique setting, the Northern California Kaiser Permanente Medical Care Program, which has a large defined population (>35,000 births/year), integrated information systems, and readily available critical information including an electronic medical record, radiology results, and laboratory test results. Using a nested case control design, we will obtain DMAsamples from infants with RDS (n~160) and controls matched by gestational age, gender, and ethnicity. Conditional multivariate logistic regression techniques will be used to evaluate for associations between these genetic variants and RDS. In the infants with RDS, we will use multivariate linear regression techniques to compare measures of RDS severity (duration of supplemental oxygen use and duration of assisted ventilation) between infants who have genetic variants and those who do not, controlling for confounders such as gestational age. Common variations in an infant's genetic code may explain why some infants develop RDS or have more severe disease. This variation may not be important unless the infant is born prematurely or has other risk factors. Knowing if an infant has any of these common variations may allow physicians to customize prevention and treatment strategies, based upon this genetic information.